Comparison of Information-Dependent Acquisition on a Tandem Quadrupole TOF vs a Triple Quadrupole Linear Ion Trap Mass Spectrometer for Broad-Spectrum Drug Screening
Comparison of Information-Dependent Acquisition on a Tandem Quadrupole TOF vs a Triple Quadrupole Linear Ion Trap Mass Spectrometer for Broad-Spectrum Drug Screening
复制标题
DOI：
10.1373/clinchem.2015.241315
复制
发表时间：
2016-01-01
影响因子：
9.3
通讯作者：
Lynch, Kara L.
中科院分区：
文献类型：
--
作者：
Thoren, Katie L.;Colby, Jennifer M.;Lynch, Kara L.
背景：具有非靶向数据采集功能的高效液相色谱-高分辨质谱仪(LC-HRMS)因其能够识别未知化合物而特别适合于一般未知药物的筛选。LC-HRMS比传统的选择性反应监测(SRM)技术具有几个优点，只要其分析性能与SRM方法相当，就可以成为理想的筛查平台。方法：我们在高分辨率质谱仪[串联四极杆飞行时间(QqTOF)]上开发了一种广谱药物筛查，它以非靶向的方式收集数据，并将其性能与以靶向方式收集数据的标称质量仪器[三重四极矩线性离子陷阱(QqLIT)]进行比较。这两种方法都使用了依赖于信息的产物离子光谱获取。我们评估了每种方法的检测下限和基质效应，并比较了它们在100例常规临床尿样中识别药物的能力。其他信息(患者处方历史、药物筛选结果等)结果：QqLIT的分析灵敏度略高于QqTOF；然而，这种差异对患者样本中的化合物鉴定没有显著影响。QQLIT在尿样中鉴定出596种药物，其中531种(%)得到确认。QqTOF确定了515种药物，其中500种(97%)得到确认。在100份尿样中，有562份确认药物(68种独特药物)，其中469份方法符合。结论：总的来说，QqTOF的检测结果与QqLIT相似，可作为一般未知药物筛查的替代方法。(C)2015年美国临床化学协会
BACKGROUND: Liquid chromatography high-resolution mass spectrometry (LC-HRMS) with untargeted data collection is especially attractive for general unknown drug screening owing to its ability to identify unexpected compounds. LC-HRMS offers several advantages over traditional selected reaction monitoring (SRM) techniques and could be an ideal screening platform as long as its analytical performance is comparable to that of SRM-based methods.METHODS: We developed a broad-spectrum drug screen on a high-resolution mass spectrometer [tandem quadrupole time-of-flight (QqTOF)] that collected data in an untargeted manner and compared its performance to a nominal mass instrument [triple quadrupole linear ion trap (QqLIT)] that collected data in a targeted manner. Both methods used information-dependent acquisition of product ion spectra. We evaluated the lower limits of detection and matrix effects for each method and compared their ability to identify drugs in 100 routine clinical urine samples. Additional information (patient prescription history, drug screening results, etc.) was used to confirm discordant results.RESULTS: QqLIT was slightly more analytically sensitive than QqTOF; however, this difference did not significantly affect compound identification in patient samples. QqLIT identified 596 drugs in the urine samples, of which 531 (89%) were confirmed. QqTOF identified 515 drugs, of which 500 (97%) were confirmed. There were 562 instances of a confirmed drug (68 unique drugs) in the 100 urine samples; the methods were concordant in 469 of these instances.CONCLUSIONS: Overall, QqTOF performed similarly to QqLIT and could serve as an alternative method for general unknown screening. (C) 2015 American Association for Clinical Chemistry